Characterization of biofilm formation in mycobacterium abscessus

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Dokic, Anja ORCID: https://orcid.org/0000-0002-7196-4689 (2021). Characterization of biofilm formation in mycobacterium abscessus. University of Birmingham. Ph.D.

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Abstract

Mycobacterium abscessus is a non-tuberculous mycobacterium (NTM) and an emerging opportunistic human pathogen associated with difficult to treat pulmonary infections, particularly in patients suffering from cystic fibrosis. Resembling other NTMs, M. abscessus is capable of forming biofilms in the environment, on medical devices and, alarmingly, in patient lungs, however not much is known about the composition and formation of this biofilm. Therefore, this work describes pellicular biofilm formation in the M. abscessus type strain (ATCC 19977) and six pulmonary clinical isolates. Using scanning electron micrographs and fluorescence microscopy it was shown that M. abscessus biofilms produce an extracellular matrix composed of lipids, proteins, carbohydrates, and extracellular DNA. Transcriptomic analysis of biofilms revealed an upregulation of pathways involved in the glyoxylate shunt, redox metabolism, and mycolic acid biosynthesis. Genes involved in elongation and desaturation of mycolic acids were highly upregulated in biofilms and biochemical analysis of mycolates revealed corresponding molecular changes. Additionally, six pulmonary clinical isolates of M. abscessus from a strain collection were biologically characterized and compared based on genetic sequences. Main differences amongst the isolates were related to variation in colony morphology, with half of the isolates presenting as smooth (presence of surface glycopeptidolipids) and half as rough (absence of glycopeptidolipids) colonies on agar. All clinical strains formed biofilms, and exhibited a lipid profile similar to the type strain. Whole genome sequencing identified that two of the strains belong to the M. abscessus subspecies M. massiliense and M. bolletii, and that the M. abscessus complex has a high degree of genetic uniformity. Together these results give us a novel understanding of biofilm formation in M. abscessus and a deeper insight into the M. abscessus complex, the understanding of which may be adapted for clinical use in treatment of biofilm infections.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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